The dominant theme of this research proposal is to provide new ways of increasing lung surfactant at the air-fluid interface of lung alveoli. Decreased synthesis, increased degradation, or both are observed in the Respiratory Distress Syndrome of the newborn, and in a number of adult equivalents. The proposal provides for a) a study of the controlling mechanisms that may govern the turn-over of available natural lung surfactant and b) a physical-chemical study of natural lung surfactant in order to provide the detailed rationale required to synthesize an articial material similar to the natural material: a) Thyroid hormones, L-thyroxine and tri-iodothyronine have been shown to be potent regulators of surfactant production. In human newborns suffering from Respiratory Distress Syndrome, decreased total serum thyroxine levels has been observed when compared to prematures delivered without respiratory distress syndrome. Better understanding of the mechanisms for the clinical and animal studies will provide information which could lead to a valuable therapeutic tool. b) Synthesis of lung surfactant has currently been completed and a better basic understanding of its physical properties and that of synthetic systems is also obtained. We are currently evaluating the physiological implications of this synthetic surfactant systems in animal models suffering from Respiratory Distress Syndrome.